Leandro Ivaldi’s scientific contributions

BACKGROUND: Results from the meta-analysis of randomized controlled studies demonstrate that the adjuvant use of probiotics enhances the rate of Helicobacter pylori (Hp) eradication, reducing concomitantly the occurrence of side effects, mainly diarrhea. Bifidobacterium animalis lactis BB12 and Enterococcus faecium L3 are two bacterial strains reported to clinically improve the rate of Hp eradication, reducing concomitantly the occurrence of side effects. METHODS: Due to our pragmatic and routine use of these two strains as an adjuvant therapy to antibiotics and proton pump inhibitors (PPIs) during attempted Hp eradication, we have analyzed retrospectively their impact on the outcome. RESULTS: Our results, obtained through a highly pragmatic clinical approach, demonstrate that the probiotic add-on therapy before and after the triple or quadruple therapy to eradicate Hp increases eradication rates and reduces side effects. Moreover, even if observed in only a small cohort of patients, the treatment seems to improve the eubiosis of the gut microbial consortium. CONCLUSIONS: In conclusion, administration of BB12 and L3 strains as an adjuvant regimen during Hp eradication therapy has better success than conventional therapy (antibiotics plus a PPI) alone.

Background: In Western countries functional dyspepsia (FD) has a prevalence of 10-20% among adults and although many drugs are currently available for use within clinical practice, FD remains an important challenge for physicians. Recently, food supplements that are ginger-based, along with other botanicals, have been proposed to be a possible natural alternative to pharmaceutical drugs to empirically counteract the symptoms of FD. Methods: We have therefore retrospectively analyzed the efficacy and safety profiles of a nutraceutical containing, in addition to a highly standardized ginger root extract, a multi-fractionated botanical obtained from Perilla frutescens leaf containing an innovative bouquet of compounds, including hydrophilic polyphenols and the lipophilic terpenoid perilla ketone. Results: The results of our single-group study, obtained from patients with a diagnosis of FD who were treated with the perilla/ginger nutraceutical, demonstrated a good efficacy profile, with a significant reduction observed in nearly all evaluated symptoms (epigastric pain, heartburn, gastric reflux, nausea, borborygmi, early satiety, diarrhea/constipation) starting from the first week of treatment that was further improved after 2 weeks. The treatment was well tolerated with very mild side effects (flatulence, meteorism, gastric burning, difficulty in falling asleep) lasting 3-4 days, which disappeared without stopping the treatment. Conclusions: Despite all the limitations of our pragmatic study, we believe that the perilla and ginger supplement we have used can be considered a valid tool for an empirical approach to treating patients with FD, especially when a non-conventional drug treatment is preferable to the patient and considered suitable by the physician.

Background: Berberine, an alkaloid obtained by extraction from Berberis spp., is a botanical that is widely used in the nutraceutical sector to control cholesterol and blood glucose levels. It is also a molecule that is effective in limiting diarrhea due to its multi-factorial properties, including its antimicrobial, gut eubiotic and antisecretive actions, and its ability to slow gut motility. In our routine clinical practice, we have suggested the use of a berberine-based nutraceutical, formulated with melatonin and depolymerized guar gum, to patients affected by functional diarrhea (FD) or by diarrhea-type irritable bowel syndrome (IBS-D). Methods: We have therefore retrospectively analyzed the clinical effect of such a nutritional supplement in these two sub-groups of patients. Results: Despite the highly pragmatic scheme of our study, our findings strongly confirm the antidiarrheal properties of berberine and recommend its use in some gut functional diseases characterized by frequent evacuation of mushy and/or watery stools. In fact, even after 30 days of treatment, the berberine-based nutritional supplement significantly reduces diarrheal events by 50-70%. After 90 days, this reduction improves to between 70 and 80%, with a reduction of more than 60% in the number of evacuations per week and with more than 50% of treated subjects demonstrating normalized, according to self-reported Bristol Stool Scale categorization, stool consistency. The product is well tolerated and adherence to the proposed therapy is good. Common side effects of the product are flatulence and meteorism, likely due to the "acarbose-like" berberine effects on gut α-glucosidase. Conclusions: Patients, especially those preferring "natural" therapy, can be successfully treated, when affected by a gut functional disease characterized by diarrhea, by berberine-based products.

Background: In medical practice, the use of rifaximin and a probiotic is quite common in patients with a diagnosis of symptomatic uncomplicated diverticular disease (SUDD), with the latter being administered at the end of the rifaximin cycle. The opportunity of having a probiotic strain (Bifidobacterium longum W11) described as being resistant to rifaximin has prompted us to use it routinely in subjects with SUDD, administering it concomitantly with rifaximin. Methods: Retrospectively, we have analyzed whether our approach conferred a real clinical advantage to patients. Results: The results seem to confirm the logic of our approach. Indeed, patients treated with rifaximin concomitantly receiving strain W11 demonstrated better clinical outcomes than subjects treated with rifaximin followed by strain W11. Moreover, we have observed that the concomitant use of a rifaximin- resistant probiotic has improved the stool consistency of most patients. Finally, the adherence to the given therapy was very different, being very high in subjects undergoing concomitant use of the W11 strain and rifaximin, and being low in the other group. This is probably because of the different duration of therapy (7 days versus 14 days) and due to the fact that after 7 days of rifaximin treatment, patients felt better and decided not to proceed with the probiotic administration. Conclusions: Despite the many biases that our retrospective analysis presents, we believe that a probiotic strain demonstrating a strong non-transferable resistance to a particular antibiotic should be used along with that specific antibiotic, at least in cases of SUDD diagnosis.

Aim Lactose and complex carbohydrates maldigestion, common food intolerances due to low gut content of α- and β-galactosidase, lead to abdominal symptoms including pain, diarrhea, bloating, flatulence, and cramping. Commonly, intolerant patients are advised by physicians to avoid the offending foods (dairy foods, cereals, beans, etc). This food-limiting option, however, has possible nutritional risks. We have therefore evaluated the impact of using pure, enteric-coated α- plus β-galactosidase on gut symptoms in intolerant subjects instead of avoidance of the offending foods. Methods Sixteen subjects intolerant to lactose and/or complex carbohydrates were enrolled and evaluated in terms of gut symptoms with 1) uncontrolled diet, 2) diet devoid of offending foods, and 3) uncontrolled diet along with pure, enteric-coated α- and β-galactosidase (DDM Galactosidase®). Results Even with the uncontrolled diet, intolerant subjects treated with DDM Galactosidase® exhibited reduced gut symptoms (bloating, flatulence, diarrhea, and constipation) significantly better than the control treatment as well as having a diet devoid of offending foods. Conclusion DDM Galactosidase® is a valid and safe optional treatment to counteract lactose and complex carbohydrate intolerance in subjects who prefer not to avoid, at least partially, offending foods.

The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31) were treated with pantoprazole and a formula (Mirgeal(®)) containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32) were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0-10). Side effects, tolerability, and compliance were also assessed. Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B) completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the two groups. Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening tolerability or compliance.